兴业证券：实体瘤TCE技术路径百花齐放 国内企业创新平台布局丰富

Core Viewpoint - TCE's efficacy and commercialization capabilities in hematological malignancies have been fully validated, but several challenges remain for its widespread application in solid tumors [1] Group 1: Current Status of TCE - A total of 12 TCE therapies have been approved globally, with 10 in the US and 6 in China; 9 are for hematological malignancies and only 3 for solid tumors [1] - The application of TCE in solid tumors faces challenges such as targeting tumor-associated antigens (TAA) without harming healthy tissues, enhancing T cell infiltration in the tumor microenvironment, and overcoming immunosuppressive cells and cytokines that lead to T cell exhaustion [1] Group 2: Design Innovations Enhancing TCE Applicability - Non-full-length bispecific antibodies and 2+1 format designs have shown promise; Amgen's DLL3/CD3 bispecific antibody has been approved for SCLC, and MSD's Gocatamig has demonstrated high tumor response rates in later-line SCLC patients [2] - The "2+1" format design allows for precise control of CD3 affinity, with Xencor's XmAb platform advancing its pipeline to Phase III clinical trials [2] - TCR therapy, exemplified by Immunocore's KIMMTRAK, targets intracellular protein antigens and has received FDA approval for uveal melanoma, with potential for expansion into other indications [2] Group 3: Strategies to Mitigate Toxicity and Enhance Efficacy - Prodrug designs are being explored to reduce off-target toxicity; Janux has validated its TCE in clinical settings, and Vir's VIR-5818 shows promising initial data in HER2-positive breast cancer [3] - Co-stimulatory signals from CD28, 4-1BB, and CD2 are expected to enhance TCE responses; Regeneron's CD28 bispecific antibody strategy has shown effectiveness but raised safety concerns [3] - Selective T cell activation targets are being developed to avoid broad T cell activation risks; AstraZeneca and LavaTherapeutics are working on TCEs that selectively target CD8+ T cells and Vγ9Vδ2 T cells [4] Group 4: Domestic Companies and Pipeline Development - Domestic companies are advancing TCE research with diverse technical paths, including CD28 co-stimulatory bispecific antibodies and TCR therapies, forming a robust pipeline [5] - Companies to watch include Zai Lab, Wuxi Biologics, Heng Rui Medicine, Bai Li Tianheng, and others, indicating a rich landscape for TCE development in solid tumors [5]